Susceptibility to experimentally induced inflammatory diseases including various forms of experimental arthritis varies substantially among inbred rat strains. For example Lewis (LEW) and Dark Agouti (DA) are generally highly susceptible to streptococcal cell wall, adjuvant and collagen arthritis, whereas Fischer (F344), Brown Norway (BN) and other strains are relatively resistant. We are interested in defining the mechanisms that functionally underlie these divergent patterns of susceptibility and resistance because this information may provide insights in human autoimmune inflammatory diseases. We have previously reported substantial differences in neuroendocrine responses in these susceptible and resistant rat strains that appear to contribute to these differences. For example, LEW rats have a deficiency in hypothalamic-pituitary-adrenal axis responsiveness compared to the F344 rats. These observations have led us to explore type 1 and type 2 cytokine expression in these rat strains. It is known that corticosteroids inhibit expression of type 1 cytokines such as gamma interferon but have much lesser effects on type 2 cytokines such as IL-4 and IL-10. In collaboration with Dr. Rachel Caspi, NEI, we have observed that autoimmune disease-prone LEW rats readily produce large numbers of gamma interferon-producing Th1 cells in response to uveitic autoantigen challenge in vivo, whereas F344 rats generate a more balanced type 1/type 2 cytokine profile (Caspi RR et al., J. Immunol. 157:2668-1675, 1996; Caspi RR et al., Eye, in press). We have suggested that these differences in cytokine expression may be in part regulated by neuroendocrine mechanisms. During the course of this work, we also developed a simplified, competitive RT-PCR method for measuring rat cytokines (Sun B et al., J. Immunol. Methods 199:193-203, 1996). Using this method, we are continuing to analyze cytokine expression.